Ectoderm barcoding reveals neural and cochlear compartmentalization

Abstract

Placodes and the neural crest are defining features of vertebrates. In this study, we investigate their lineages in mice using in utero approaches. We demonstrated that nanoinjection at embryonic day 7.5 targeted the ectoderm, including the future nervous system, placodes, and neural crest, allowing highly efficient manipulation of the future nervous system and inner ear. By using heritable DNA barcodes and high-throughput next-generation single-cell lineage tracing, we elucidated convergent differentiation pathways and identified distinct nervous system-, neural crest-, and otic placode-derived lineages. Clonal analyses identified early neural and cochlear compartmentalization, linking differentiated cell types to their progenitors or cellular siblings. This provides foundational insights for neuroscience and developmental biology.